Effect of Silibinin In Vivo on the Pharmacokinetics of Nevirapine in Rats
10.13748/j.cnki.issn1007-7693.20230944
- VernacularTitle:水飞蓟宾对奈韦拉平在大鼠体内药动学的影响
- Author:
Peipei PAN
1
;
Jun LUO
2
,
3
;
Shuanghu WANG
2
,
3
;
Peiwu GENG
4
,
5
Author Information
1. Department of Pharmacy, Taizhou Central Hospital, Taizhou 318000, China
2. Department of Pharmacy, Taizhou Women and Children'
3. s Hospital of Wenzhou Medical University, Taizhou 318000, China
4. Department of Pharmacy, People&rsquo
5. s Hospital of Lishui, Lishui 323000, China
- Publication Type:Journal Article
- Keywords:
nevirapine； silibinin； pharmacokinetics；UPLC-MS/MS
- From:
Chinese Journal of Modern Applied Pharmacy
2024;41(13):1758-1764
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE :To explore the effect of single dose and multiple doses of silibinin on the in vivo pharmacokinetics of nevirapine in rats.
METHODS
Thirty male SD rats were randomly divided into blank control group, multiple administration of low-dose group(30 mg·kg−1) , multiple administration of high-dose group(100 mg·kg−1), single administration low-dose group(30 mg·kg−1) , and single administration high-dose group(100 mg·kg−1). Blood samples were collected to determine the concentration of nevirapine and its metabolites in rat plasma after an oral administration of 10 mg·kg−1 nevirapine. The kinetic parameters of nevirapine and its metabolites in each group were calculated by DAS and analyzed statistically.
RESULTS
Compared with the blank control group, multiple doses of 100 mg·kg−1·d−1 silibinin significantly increased the AUC of nevirapine by 61.78%, Cmax by 124.62% and decreased the clearance rate to 64.11%; multiple doses of 30 mg·kg−1·d−1 silibinin significantly increased the Cmax of nevirapine by 84.85%; a single dose of 100 mg·kg−1 or 30 mg·kg−1 silibinin significantly increased the Cmax of nevirapine by 65.19% and 32.12%, respectively. The metabolic ratio of 12-hydroxy-nervirapine was decreased by 31.5% by multiple doses of 100 mg·kg−1·d−1 silibinin where the pharmacokinetic parameters of 4-carboxyl-nervirapine remained unchanged.
CONCLUSION
Silibinin significantly affects the pharmacokinetics of nevirapine in rats. The drug-drug interaction should be considered when nevirapine and silibinin are concomitant.
